SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways

Brian Jonas, Martin L. Privalsky

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

N-CoR and SMRT are corepressor paralogs that partner with and mediate transcriptional repression by a wide variety of metazoan transcription factors, including nuclear hormone receptors. Although encoded by distinct genetic loci, N-CoR and SMRT share substantial sequence interrelatedness, form analogous assemblies with histone deacetylases and auxiliary factors, can interact with overlapping sets of transcription factor partners, and exert overlapping functions in cells. SMRT is subject to negative regulation by MAPK signaling pathways operating downstream of growth factor and stress signaling pathways. We report here that whereas activation of MEKK1 leads to phosphorylation of SMRT, its dissociation from its transcription factor partners in vivo and in vitro, and its redistribution from the cell nucleus to a cytoplasmic compartment, N-CoR is refractory to all these forms of regulation. In contrast to this MAPK cascade, other signal transduction pathways operating downstream of growth factor/cytokine receptors appear able to affect both corepressor paralogs. Our results indicate that SMRT and N-CoR are embedded in distinct regulatory networks and that the two corepressors interpret growth factor, cytokine, differentiation, and prosurvival signals differently.

Original languageEnglish (US)
Pages (from-to)54676-54686
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
StatePublished - Dec 24 2004

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Co-Repressor Proteins
Intercellular Signaling Peptides and Proteins
Transcription Factors
Phosphotransferases
Nuclear Receptor Co-Repressor 2
Growth Differentiation Factors
Signal transduction
Phosphorylation
Cytokine Receptors
Genetic Loci
Histone Deacetylases
Growth Factor Receptors
Cytoplasmic and Nuclear Receptors
Cell Nucleus
Refractory materials
Signal Transduction
Chemical activation
Cells
Cytokines

ASJC Scopus subject areas

  • Biochemistry

Cite this

SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways. / Jonas, Brian; Privalsky, Martin L.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54676-54686.

Research output: Contribution to journalArticle

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